Maxi-K channels: structure, characteristics, biological process and principal blockers and activators. A general overview.

Abstract

Maxi-K also known as BK channels, Slo1 or KCa1.1 channels, are one type of calcium-activated potassium channels that have large single channel conductance of 100–300 pS . Their most important physiological property is dual regulation through membrane voltage and intracellular Ca 2+ . 1 The complexity of this channel function mirrors the complexity of its protein structure. The amino acid sequence includes the integral membrane pore shared by all K + channels, the integral membrane voltage sensor domains present in voltage-dependent channels, and a cytoplasmic domain (CTD) consisting of approximately 800 amino acids per subunit, which accounts for the C-terminal two thirds of the entire channel. The CTD structure confers upon the BK channel its ability to respond to changes in intracellular Ca 2+ . 2-5 It is also the source of functional heterogeneity through alternate splicing, polymorphisms, phosphorylation, and protein interactions, which modulate BK channel activity. 5-8 These channels modulate several physiological events, like blood pressure, smooth muscle relaxation or electrical tuning of hair cells in the cochlea and have a leading role in many pathophysiological conditions such as epilepsy, ischemic stroke, cognitive disorders, and the behavioral response to alcohol, to give only a few examples. 9, 10 Studies involving activation and inactivation with pharmacological and genetic tools, including global, and tissue-specific knockouts, have implicated Maxi-K channels in cardiac function, neuroprotection, and cardio-protection from ischemia-reperfusion (IR) injury, in addition to IR-induced inflammation and mucosal barrier disruption in the small intestine. 11 It is also known that Maxi-K channels function as neuronal calcium sensors and contribute to the control of cellular excitability and the regulation of neurotransmitter release. 9 Numerous Maxi-K channel blockers and activators are used to identify these channels and study their functions. Some of the most common